Preparation of rutin colloidal silicon dioxide solid dispersion and bioavailability in vivo / 中草药

ABSTRACT

Objective: To prepare the solid dispersion of rutin colloidal silicon dioxide (Ru-CSD-SD) and to promote the rutin oral absorption function, in order to evaluate its in vivo and in vitro oral absorption. Methods: Composition and method of Ru-CSD-SD were investigated by single factor test; Equilibrium solubility experiments, differential thermal analysis (DSC), and X-ray diffraction (XRD) were used to determine the Ru-CSD-SD. Cumulative dissolution rates and pharmacokinetic parameters of Ru-CSD-SD were evaluated by drug releasing in vitro and in vivo. Results: The preparation conditions of Ru-CSD-SD was selected on the basis of single factor test Colloidal silicon dioxide AEROPERL® 300 pharma (CSD300) was used as carrier, the ratio of drug (rutin) and carrier (CSD300) was 1∶2, and the method was solvent evaporation. After preparation of Ru-CSD-SD, the equilibrium solubility of rutin increased by 2.7 times from 72.69 to 198.73 mg/L; The DSC and XRD were indicated that rutin existed in the solid dispersions at amorphous form. And cumulative dissolution rates of Ru-CSD-SD reached (82.01 ± 1.04)% in 5 min. After oral administration of rutin ordinary tablets and Ru-CSD-SD, t1/2 were 1.078, and 10.899 h, tmax were 1.5, and 0.5 h, and Ru-CSD-SD of Cmax (103.45 μg/mL) was 15.46 times of ordinary tablets (6.69 μg/mL). Ru-CSD-SD of AUC0-∞ (170.406 μg∙h/mL) was 12.20 times of ordinary tablets (13.965 μg∙h/mL). Conclusion: The Ru-CSD-SD with CSD300 can increase the solubility, dissolution rate, and bioavailability.